The following version of this book was used to create this guide: Kelly, Lynne. Song For a Whale. Delacorte Press, 2019.

The novel is divided into 48 chapters, the majority of which are from the first-person perspective of Iris, a 12-year-old Deaf girl living in Houston who finds herself bonding with a whale, Blue 55, whose song cannot be understood by other whales.

The novel begins with Iris talking to her grandfather about a whale that lent her her name. Events immediately jump forward to the present-day; her grandfather has since died, and Iris is a student at a school where there are no other Deaf students. Her science class is a respite from the alienation she feels, and she learns about Blue 55 there. Blue 55 is a whale whose voice is a different frequency from the other whales, meaning none of the other whales can understand him. At lunch that day, she tries to engage with classmates about the whale, but Nina, a classmate who tries to learn sign language to communicate with Iris, keeps trying to butt in and incorrectly signs to Iris; frustrated, Iris pushes Nina, leading to her suspension from school.

Iris arrives home, surveying the antique radios that she has a passion for restoring in her room. However, her mother takes them away for the weekend as punishment for her behavior at school. Grounded, she looks up more info on Blue 55, leaving a comment on the page of a sanctuary trying to locate him suggesting he may be deaf. Later, they visit Iris's grandmother, who is also Deaf; she has been consumed by grief since Grandpa's passing. Iris returns to school and starts restoring her radios again. She meets her good friend, a Deaf boy named Wendell, and tells him about Blue 55 and how she wants to find a way to communicate with him.

Iris prints out sheet music corresponding with different whale songs, then takes it to the band teacher at her school so that the band can record a song at Blue 55's frequency. She edits it herself, combining the song with sounds of other animals at Blue 55's sanctuary, and sends it to a worker named Andi at the sanctuary. Iris visits the school Wendell's mother works at, Bridgewood, which has a robust Deaf population. Meanwhile, the sanctuary responds that they will play Iris's song in an attempt to communicate with Blue 55; Iris tells her family about it, wanting to go up and visit the sanctuary, but they seem not to understand her passion and do not want to go. Andi writes Iris back and says not to come immediately as she would not be able to go on the expedition to tag him anyway. Iris's father comes in and shows her recordings of whale songs he listened to when he was a child.

Iris, determined to get to Alaska to see Blue 55, sells her radios to finance the trip, but finds herself unable to withdraw large sums of money from the bank without a parent. She goes to visit Grandma and tells her about it and Grandma suggests they go on an Alaskan cruise to see the whale together, unbeknownst to Iris's parents. They set off together and eventually board the cruise ship. Onboard, Grandma seems much more colorful and relaxed, telling Iris stories about her and Grandpa's experiences aboard cruises themselves.Iris attends a lecture by the naturalist onboard, Sura, about Alaskan wildlife, and meets Bennie, her daughter, who is about Iris's age. The two grow close. Iris shows Bennie her song and the two attend a whale watching put on by Sura together. Bennie shows Iris how to modulate her own voice to get it to Blue 55's pitch, and they add it to the song. Shortly thereafter, Iris and Grandma go on a boat cruise to see Alaskan glaciers, something Grandma had always wanted to do with Grandpa.

Later onboard the ship, Grandma commands a rapt crowd at karaoke by signing the songs, just like her and Grandpa used to do. Then, Blue 55 is spotted heading down toward Oregon instead of toward Alaska; Grandma and Iris decide they will try to intercept him there, changing their itinerary. Andi writes Iris with the news that Lighthouse Bay in Oregon does not want to play Iris's song for Blue 55. All the while, Iris's parents email her, worried.

Iris is inspired to try to build a waterproof Bluetooth speaker to play her song for Blue 55 after seeing a man using one in a pool onboard the cruise. At the cruise's next stop, Iris visits the junkyard and finds the parts to make one, and does. Soon after, Grandma and Iris take the train and then a shuttle to Lighthouse Bay. Once there, Iris runs toward the sanctuary to see Andi celebrating on a boat, presumably after having tagged Blue 55. Then, Iris sees him jump out of the water, and she jumps in herself, swims toward him, plays his song on her speaker, and touches him. A chapter from his perspective describes his relief at hearing it. Andi intercepts her and they meet her family, who have gathered this is where she is and traveled to find her.

Back home, Grandma and Iris convince Iris's mother to let her go to Bridgewood next year, the school with the Deaf population. Grandma, having processed her grief onboard the cruise, will be living on a ship full-time next year. Blue 55 has less trouble communicating with other animals now that he has heard Iris's song.